Abstract In a state of lymphopenia, naive and memory CD4 T cells compete with each other for expansion at the expense of naive T cells. This competition prevents the proliferation as well as the phenotypic and functional conversion of naive T cells to “memory-like” T cells and may consequently prevent immune pathology frequently associated with lymphopenia-induced proliferation of naive cells. However, in T cell replete mice, memory T cells do not compete with naive T cells, indicating independent homeostatic control of naive and memory CD4 T cells in conditions that do not involve profound lymphopenia. Moreover, within the memory compartment, subsequent generation of new memory T cells precludes the survival of memory-like T cells. Thus, memory T cells have a major role in the control of lymphopenia-induced proliferation of naive cells because they inhibit both the generation of memory-like T cells and their persistence within the memory compartment.